Is Adoptive Cellular Therapy With Non-T-Cell Immune Effectors the Future?

Success from checkpoint blockade and adoptive cell therapy has brought a new hope in cancer immunotherapy. Adoptive cell therapy involves the isolation of immune cells, ex vivo activation and/or expansion, and reinfusion into the patients, and their effect can be dramatically increased by the incorporation of chimeric antigen receptors specific to molecules expressed on tumor cells. Chimeric antigen receptor T cells have shown exciting results in the treatment of liquid malignancies; nevertheless, they suffer from limitations including severe adverse effects such as cytokine release syndrome and neurotoxicity seen in patients as well as a potential for causing graft-versus-host disease in an allogeneic setting. It is thus imperial to explore innate immune cells including natural killer cells, macrophages, natural killer T cells, and γδ T cells. Here, we provide a broad overview of the major innate immune cells and their potential for adoptive cell therapy and chimeric antigen receptor engineering.